Our results show that otherwise disparate developmental neurotoxicants converge on common cellular pathways governing the acquisition and programmed death of neural cells, providing a specific link to cell deficits. Our studies suggest that identifying the initial
mechanism of action of a developmental neurotoxicant may be strategically less important than focusing on the pathways that converge on common final outcomes such as cell loss. (c) 2012 Elsevier Inc. All rights reserved.”
“The muscleblind-like (MBNL) proteins CHIR-99021 cost 1, 2, and 3, which contain four CCCH zinc finger motifs (ZF1-4), are involved in the differentiation of muscle inclusion by controlling the splicing patterns of several pre-mRNAs. Especially, MBNL1 plays a crucial role in myotonic dystrophy. The CCCH zinc finger is a sequence motif found in many RNA binding proteins and is suggested to play an important role in the recognition of RNA molecules. Here, we solved CYT387 the solution structures of both tandem zinc finger (TZF) motifs, TZF12 (comprising ZF1 and ZF2) and TZF34 (ZF3 and ZF4), in MBNL2 from Homo sapiens.
In TZF12 of MBNL2, ZF1 and ZF2 adopt a similar fold, as reported previously for the CCCH-type zinc fingers in the TIS11d protein. The linker between ZF1 and ZF2 in MBNL2 forms an antiparallel beta-sheet with the N-terminal extension of ZF1. Furthermore, ZF1 and ZF2 in MBNL2 interact with each other through hydrophobic interactions. Consequently, TZF12 forms a single, compact global fold, where ZF1 and ZF2 are RG7420 datasheet approximately symmetrical about the C2 axis. The structure of the second tandem zinc finger (TZF34) in MBNL2 is similar to that of TZF12. This novel three-dimensional structure of the TZF domains in MBNL2 provides a basis for functional studies of the CCCH-type zinc finger motifs in the MBNL protein family.”
“We generated four HIV-1 cultures that are resistant to a peptide fusion inhibitor corresponding to the first heptad repeat of gp41 in order to study mechanisms of resistance and gain insights into envelope glycoprotein-mediated membrane
fusion. Two genetic pathways emerged that were defined by acquisition of a specific mutation in either the first or second heptad repeat region of gp41 (HR1 or the HR2, respectively). Each pathway was enriched in mutations that clustered in either HR2 and V3 or in HR1 and residues in or near CD4 contact sites. The gp41 mutations in both pathways not only accounted for resistance to the selecting HR1 peptide but also conferred cross-resistance to HR2 peptide fusion inhibitors and enhanced the stability of the six-helix bundle formed by the self-assembly of HR1 and HR2. The gp120 mutations alone enhanced fusion but did not appear to directly contribute to resistance. The implications of these findings for resistance mechanisms and regulation of envelope-mediated fusion are discussed.”
“Mitochondria possess a complex architecture with two membranes.